6,7-epoxygeranyl ethers of oxygen heterocyclic compounds

ABSTRACT

6,7-EPOXYGERANYL ETHERS OF THE FORMULA   2-(H3C-),3-((R)M-Y-(CH2)N-O-CH2-CH=C(-CH3)-(CH2)2-)-   OXIRANE   WHEREIN N=0 TO 3 Y=5 OR 6 MEMBERED DI- OR TRIVALENT HETEROCYCLIC GROUP CONTAINING UP TO 2 ATOMS OF OXYGEN AND UP TO 1 ATOM OF SULFUR; R= HYDROGEN, ALKYL, PERCHLOROALKYL OR ALKOXY OF UP TO 4 CARBON; AND M=1 OR 2; ARE MODIFIERS OF INSECT GROWTH AND DEVELOPMENT

United States Patent OF THE DISCLOSURE 6,7-Epoxygeranyl ethers of theformula wherein Y=5 or 6 membered dior trivalent heterocyclic groupcontaining up to' 2 atoms of oxygen and up to 1 atom of sulfur;

R: hydrogen, alkyl, perchloroalkyl or alkoxy of up to 4 carbons; and

are modifiers of insect growth and development.

' BACKGROUND OF THE INVENTION Field of the Invention I This'inventionconcerns certain 6,7-epoxygeranyl ethers 'and their use to control thegrowth and development of harmful insects.

Prior Art Dutch patent application 69/ 10,519 opened for inspection onOctober 13, 1970, Bowers, US. Pat. 3,563,982, and Science 164, 323(1969), disclose certain aromatic ethers of 6,7-epoxygeraniol as insectcontrol agents. They are not the same as the compounds of thisinvention.

Description of the Invention It has now been found that certain oxygenheterocyclic ethers, namely, 6,7-epoxygeranyl ethers of the formula Rarecapable of interfering with the normal growth and development of harmfulinsects.

The preparation of the compounds is exemplified by the 3,823,162Patented July 9, 1974 CtE reaction of2-methyl-4-hydroxymethyl-1,3-dioxolane with 6,7-epoxygeranyl bromide:

6,7-epoxygeranyl b i 2-methyl rom de -hydroxymethyl 1,3-dioxolane O l\CH| OCHFI 2-methyl-4(6,7-eporygeranyloxymethyD- 1,3-dloxolane Theintermediate geranyl bromide is preferably prepared by the method ofWagner-Jauregg and Arnold [Ann. 529, 274 (1937)]. Technical gradegeraniol can be used but the low yields usually obtained make itpreferable to employ a high grade of geraniol. This leads to a geranylbromide of sufficient purity to be used directly in the next synthesisstep.

The crude geranyl bromide prepared by the preferred procedure above isepoxidized by reaction with m-chloro; perbenzoic acid following theprocedure of F. M. Pallos et al. [Nature, 232, 486 (1971)].

The procedure of H. S. Hill et al. [1. Am. Chem. Soc. 50, 2242 (1928)]was followed to obtain a mixture of 2- methyl-4-hydroxymethyl 1,3dioxolane and 2-methyl-5- hydroxy-1,3-dioxane. These were separated byconverting the alcohol mixture to the benzoate derivative, using benzoylchloride and pyridine. Crystallization from petroleum ether (BO-60) gavea solid benzoate, rn.p. -85 C., and an oily benzoate. There werenumerous difierences in the IR and NMR spectra.

Each ester was saponified with sodium hydroxide in water at 70-80 C. Thesolid benzoate gave rise to 2- methyl-S-hydroxy-1,3-dioxane, b.p. 64-65C. (10 mm.); IR (film), 2.90; (OH); NMR (CD01 64.74 (q, 1, 1:5, OCHMeO),3.92 (m, 4, CH O), 3.57 (m, 2, CHOH), 1.31 (d, 3, 1:5, CH

The liquid benzoate gave 2-methyl-4-hydroxymethyl- 1,3-dioxolane, b.p.78-83 C. (10 mm.); IR (film), 2.90 (OH); NMR (CDCl 549-53 (In, 1,OCHMeO), 2.8- 4.4 (m, 6, CH O, CHOH), 1.3-1.5 (m, 3, CH

Synthesis of intermediates in preparing the compounds of the variousexamples, as in Examples 10-19, is given herewith.

-A. 2,2-dimethyl-1,3-dioxolane-4-methanol (I).

H O py 01131 3 0 I II The alcohol I was acetylated as follows: Acetylchloride (160 g.) was added over a period of 1 hr. to a solution of 254g. of the ketal I in 160 g. of pyridine and 750 ml. of benzene whilekeeping the reaction mixture at -5 by ice-cooling. After 3 hr. at 0, themixture was filtered and the solids were promptly washed with benzene.The filtrate was concentrated and the residual oil was distilled to give321 g. of liquid, b.p. 79-81 (11 mm.), 96% yield; IR (filIIl)-5.74,u(C:O); NMR (CDCl;,): 63.5-4.4 (m, 5, CHgO, CH0), 2.03 (s, 3, CH CO),1.39, 1.31 (2s, 6, CH

C. 2-t-Butyl-1,3-dioxo1ane-4-methyl Acetate (III) The following is anexample of the exchange reaction which has been used with a number ofaldehydes to give dioxolanes such as III.

A mixture of 19.1 g. of the acetate II, 35 g. of pivaldehyde, 0.5 g. ofp-toluenesulfonic acid hydrate, and 100 ml. of benzene Was refluxed forhr. The solution was washed with satd sodium bicarbonate solution, driedover potassium carbonate, and distilled to give 18.4 g. (83% yield) ofliquid, b.p. 97-98 (11 mm.), IR (film) 5.71;. (0:0); NMR (CD01 64.67,4.59 825, 1 (cis, trams), OCHtBuO], 3.6-4.3 (m, 5, CH O, CH0), 2.10 (s,3, CH CO), 0.92 [s, 9, C(CH D. 2-t-Buty1-1,3-dioxolane-4-methanol (1V) OLiAlHa CH H3 0 H O III IV The acetate group can be removed by basichydrolysis but the hydride reduction procedure is preferred becausenon-aqueous work-up is used.

To a suspension of 2.0 g. of lithium aluminum hydride in 50 ml. of THFwas added 16.5 g. of the acetate III at 0-l0. After 30 min. at 0, 2.0ml. of water is cautiously added, followed by 2.0 ml. of 15% aq. sodiumhydroxide, and 6.0 ml. of water. The solids were removed by filtrationand were thoroughly washed with ether. Distillation of the filtrate gave11.6 g. of liquid, b.p. 87-89" (11 mm.), 89% yield, IR (fi1m)2.9 (OH);NMR (CDCl )2s(1H) 4.69, 4.606 (OCHtBuO); m(5H) 3.5-4.3 (CH O, CHO);m(1H) 2.7 (OH); s(9H) 0.96 a)a)- The above sequence was applied to theexamples in which the Z-substituent was: iso-butyl, sec-butyl, t-butyl,diethyl, ethyl, and also to the oxathiolane example 20 where thestarting material was 3-mercaptopropan-1,2- diol.

SPECIFIC EMBODIMENTS OF THE INVENTION In the following examples, whichare illustrative and not limitative, all parts and percentages are byweight unless specified otherwise.

EXAMPLE 1 R 2-Methyl-4(6,7-epoxygeranyloxymethyl)-1,3-dioxolane n=1 Y=R= CH1 0 To a solution of 9.4 g. mmol) of2-methyl-4-hydroxymethyl-l,3-dioxolane in 50 ml. of tetrahydrofuran(THF) at 70 C. was added 50 ml. of 1.6M solution of n-butyllithium inhexane. The mixture was stirred at 70 C. for 15 minutes and then 16.0 g.of crude 6,7- epoxygeranyl bromide was added. The mixture was stirred at25 C. for 22 hours and at 50 C. for 4 hours. The reaction mixture waspoured into water and the product extracted into ether. The combinedether extracts'were dried over potassium carbonate and concentratedunder reduced pressure. Partial evaporative distillation at 70 C./0.02mm. yielded some unreacted epoxygeranyl bromide. Further distillation atC./ 0.02 mm. gave 5.61 g. of 2methyl-4-(6,7-epoxygeranyloxymethyl)-1,3-dioxolane: IR (film) 5.95(C:C), 11.5[L (epoxide); NMR (CDCl 65.43 (m, 1, vinyl), 5.10 (m, 1, OCI;I CH O), 3.7-4.3 (m, 5, CH O, CHO'), 3.3-3.6 (m, 2, CH O), 2.7 (t, 1,1:6, epoxide H), 2.0-2.4 (m, 2, allylic CH 1.71 (m, 5, allylic CHepoxide CH 1.2-1.5 (m, 9 epoxide CH OCCH O); tlc, single spot on silicagel, 3:1 benzenezether.

EXAMPLE 2 2-(6,7-Epoxygeranyloxymethyl) tetrahydrofuran The procedure ofExample 1 was followed using 8.15 g. (80 mmol) of tetrahydrofurfurylalcohol in place of the 2-methyl-4-hydroxymethy1-1,3-dioxolane. Theproduct was isolated by column chromatography on Florisil, followed byevaporation distillation at C./0.04 mm.: IR (film), 5.98 (O:C), 11.4(epoxide); NMR (CDCl 65.42 (m, 1, vinyl H), 3.7-4.2 (d+m, 5, CH O, CH0),3.41 (d, 2, 1:5, CHgO), 2.70 (t, 1, 1:6, epoxide H), 1.5-2.4 (m, 11),1.26, 1.22 (2s, 6, epoxide CH EXAMPLE 32-Ethyl-4-(6,7-epoxygeranyloxymethyl)1,3-dioxolane The procedure ofExample 1 was applied to 10.6 g. (80 mmol) of2-ethyl-4-hydroxymethyl-1,3-dioxolane in place of the Z-methyl homolog.In addition, 10 ml. of hexamethylphosphoramide was used as cosolvent andno heating was required. The product, 5.7 g. of 2-ethyl-4-(6,7-epoxygeranyloxymethyl)-1,3-dioxolane, was obtained by evaporativedistillation at C. (0.04 mm.); IR (film), 6.00 (C:C); 11.5 (epoxide);NMR (CD01 65.41 (m, 1, vinyl H); 4.9 (m, 1, OCHEtO); 3.3-4.3 (m, 7, CHO, CH0); 2.69 (t, 1, 1:7, epoxide H); 1.27, 1.22 (2s, 6, epoxide CH 0.92(t, 3, 1:7, CH

Using the procedure of Example 1, the following heterocyclic alcoholswere reacted with 6,7-epoxy'geranyl bromide under the conditions shownto give compounds of the invention wherein the values for n, Y and R areas indicated.

The compounds of the invention have activity as juve-.

nile hormone mimics in certain harmful insects and therefore haveutility as insect control agents.

Tenebrio (yellow mealworm assay). Tenebrio molitor is a beetle whichinfests stored grain and is a commonly used test species. The compoundis dissolved in acetone and the solution is applied to the abdomen of ayoung pupa from which the adult insect develops. The ED is the amount ofcompound necessary to severely deform half of the test animals used.These insects will not live or reproduce.

Aedes aegypti (mosquito). The compound is dissolved or suspended inwater and newly hatched larvae are reared in the medium. Suppression ofadult emergence is the criterion of activity. The EC is theconcentration at which only 50% of the larvae emerge as adults.

- Biological activity is given in Table II.

TABLE II Tenebrio EDaoI 1 g.

Other data Granary weevil-400% control at 1,000 p.p;m.; confused flourbeetle-88% control at 1,000 p.p.m.

Granary weevil-77% control at 1,000 p.p.m.; confused flour beetle72%control at 1,000 p.p.m.

Mosquito Eon-0.15 p.p.m.; granary weevil-100% control at 1,000 p.p.m.;confused flour beetle-94% control at p.p.m.

Granary weevil-100% control at 1,000 p.p.m.; confused flour beetle-94%control at 1,000 p.p.1n.

Mosquito Eco-0.62 p.p.m:

Mosquito EON-0.37 p.p.m.-

Insecticidal compositions can be prepared by mixing an eflective amountof one or more of the compounds in a suitable carrier depending on theparticular mode of application. They can be made up in various formscustomary in insect pest control, such as emulsions, suspensions,solutions, powders and aerosols. In general, such preparations can inaddition to the active ingredient contain the customary auxiliaryagents. The compound according to the invention canbe the only activeingredient, but can be processed also together with one or more otheragents which have more or less the same type of purpose. The additivesused can be organic solvents, such as sesame oil, solvents of the xylenetype, petroleum fractions, etc.; water; emulsifiers; surfactants;talcum, pyrophyllite, kieselguhr, gypsum and/or clay; propellants suchas dichlorodifluoromethane, etc. The concentration of active material insuch preparations can vary within wide limits, but in general should notbe much higher than about based on the total weight of the preparation.

Preferably the concentration shouldbe about 0.1 to about 1.0% by weightof the total composition.

CLAIMS The embodiments of the invention in which an exclusive propertyor privilege is claimed are defined as follows: M w

1. A compound of the formula 1 ocHm-Y-R...

2. The compound of Claim 1 in which n=1,

R=CH 2-methyl-4(6,7 epoxygeranyloxymethyD-1,3-di oxolane.

3. The compound of Claim 1 in which n=0,

R=C H 2-ethyl-5-(6,7-epoxygeranyloxy) 1,3-dioxane. '4. The compound ofClaim 1 in which n--1,

R=C H 2-ethyl-4-(6,7 epoxygeranyloxymethyl)-1,3-di- ,oxolane. ReferencesCited FOREIGN. PATENTS 2,148,183 4/1972 Germany.

DONALD G. -DAUS, Primary Examiner J. H. TURNIPSEED, Assistant ExaminerUS. 01. XR. 260-327, 340.9, 345.9, 347.8; 424-278, 285

